Separation of a population of human T lymphocytes that bind prostaglandin E2 and exert a suppressor activity.
Separation of a population of human T lymphocytes that bind prostaglandin E2 and exert a suppressor activity.
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分离结合前列腺素 E2 并发挥抑制活性的人类 T 淋巴细胞群。
作者：
A. Fischer;F. Le Deist;A. Durandy;C. Griscelli
前列腺素E2 （PGE2）是一种有效的免疫功能抑制剂。pge2介导的抑制可能有两种机制：一种是直接抑制产生白细胞介素2的T细胞；第二种是由非特异性抑制性T淋巴细胞的激活介导的。我们之前的研究表明，PGE2可以直接激活人T淋巴细胞，抑制淋巴细胞增殖和B淋巴细胞成熟。本文描述了10%至30%的人外周血T淋巴细胞与包裹白蛋白- sepharose的不溶化PGE2的结合。结合PGE2的T淋巴细胞（PGE2 +）可以通过添加血清和轻摇珠来洗脱。以下数据表明了这种结合的特异性：i) T淋巴细胞经过一夜的孵育后，对PGE2失去了敏感性，失去了对PGE2的亲和力；ii) PGE2预孵育T淋巴细胞阻断其结合；iii) PGE2(+) T细胞在孵育24小时后结合PGE，而PGE2(-) T细胞不结合PGE。一些T细胞绑定白蛋白,只有一小部分(7 - 9%)绑定6-keto-prostaglandin F1 alpha-coated珠子。在PGE2(+) T细胞中，OKT8+细胞的百分比略有增加。尽管在有丝分裂原或抗原刺激下，与PGE2（-）无亲和关系的T细胞（PGE2(-)）和未分离的T淋巴细胞一样增殖，但PGE2（+）亚群的增殖反应较差。此外，PGE2(+) T淋巴细胞对有丝分裂原或同种异体细胞诱导的淋巴细胞增殖以及美洲商陆有丝分裂原驱动的B细胞成熟为含ig细胞具有很强的抑制活性。在这些实验中，PGE2(-) T淋巴细胞未显示出明显的抑制活性。PGE2（+）亚群介导的抑制并非继发于PGE2从微珠中释放的携带，因为其抑制活性不会因添加抗PGE2血清而改变。PGE2(-) T淋巴细胞对PGE2对细胞增殖的抑制作用不敏感。这些结果表明，外周血T淋巴细胞的一个给定功能亚群与PGE2结合，并且至少其中一些被激活为抑制性T细胞。pge2活化T抑制亚群与其他功能上定义的抑制性T细胞之间的关系仍有待澄清；然而，这表明PGE2可以通过激活可识别的抑制性T细胞作为免疫调节剂。
Prostaglandin E2 (PGE2) is a potent inhibitor of immune functions. Two possible mechanisms of PGE2-mediated suppression have been proposed: one is a direct inhibitory effect exerted on interleukin 2-producing T cells; the second is mediated by the activation of nonspecific suppressor T lymphocytes. We previously showed that PGE2 can directly activate human T lymphocytes to suppress lymphocyte proliferation and B lymphocyte maturation. Herein is described the binding of 10 to 30% of human peripheral blood T lymphocytes to insolubilized PGE2 coated to albumin-Sepharose. The T lymphocytes that bound PGE2 (PGE2(+] could be eluted by the addition of serum and gentle shaking of the beads. The following data indicated the specificity of the binding: i) T lymphocytes after an overnight incubation, a condition known to abolish sensitivity to PGE2, lost their affinity for PGE2; ii) preincubation of T lymphocytes with PGE2 blocked the binding; iii) PGE2(+) T cells bound PGE after a 24-hr incubation, whereas PGE2(-) T cells did not. Few T cells bound albumin, and only a small percentage (7 to 9%) bound 6-keto-prostaglandin F1 alpha-coated beads. Among PGE2(+) T cells, there was a slight increase in the percentage of OKT8+ cells. Although T cells that had no affinity for PGE2 (PGE2(-] proliferated as well as unseparated T lymphocytes when stimulated with mitogens or antigens, the proliferative response of the PGE2(+) subset was poor. Moreover, PGE2(+) T lymphocytes did exert a strong suppressor activity on mitogen- or allogeneic cell-induced lymphocyte proliferation as well as on pokeweed mitogen-driven B cell maturation into Ig-containing cells. PGE2(-) T lymphocytes were shown not to exert a significant suppressor activity in these assays. The PGE2(+) subset-mediated suppression was not secondary to a carry-over of PGE2 released from the beads, because its suppressor activity was not altered by the addition of an anti-PGE2 serum. Moreover, PGE2(-) T lymphocytes were not sensitive to the inhibitory activity on cell proliferation of PGE2. These results indicate that a given functional subset of peripheral blood T lymphocytes binds PGE2, and that at least some of them are activated into suppressor T cells. The relationship between the PGE2-activatable T suppressor subset and other functionally defined suppressor T cells remains to be clarified; it is suggested, however, that PGE2 can act as an immunoregulator through the activation of identifiable suppressor T cells.